Amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, is a chronic and progressive illness that leads to paralysis and ultimately death. There are no known cures, and the only FDA-approved method for treating the disease is a drug that may extend life between three and six months, said Brian Kaspar, the study's lead author and an assistant professor of pediatrics at Ohio State University.
In the study, some of the mice were treated with a combination of exercise and therapy with a gene known to help protect motor neurons.
"The combined therapy nearly doubled the lifespan of mice with ALS," said Kaspar.
Mice that had ALS but received no treatment lived an average of 120 days. However, mice that were allowed to exercise and also received gene therapy lived an average of 210 days. Healthy mice usually live for one or two years.
"Somehow, the two treatments complement each other and benefit the mouse," said Kaspar, who is also an investigator with the Center for Gene Therapy at Columbus Children's Research Institute.
He presented the work November 14 in Washington, D.C., at the annual meeting of the Society for Neuroscience.
In the current study, the researchers looked at the effects of exercise both with and without additional gene therapy treatment. A group of mice serving as a control had ALS but received no treatment.
The study also showed that mice with ALS benefited from exercise more if they began earlier in life. Some mice began exercise treatment (with no gene therapy) at 40 days of age, while other mice didn't start to exercise until 90 days of age.
The mice that started exercising when they were younger lived about a month longer than the control mice, while the mice that began exercising at 90 days of age lived an average of 11 days longer than the control mice.
"The earlier the mice could exercise, the better they did," Kaspar said.
Studies of other neuronal diseases, such as Parkinson's and Huntington's, have suggested that exercise may actually prevent neurons from dying.
In related work, Kaspar and his colleagues found that gene therapy extended mouse survival by about 20 to 25 days. The gene they used, insulin-like growth factor 1 (IGF-1), produces a hormone by the same name. This hormone helps protect motor neurons and also stimulates muscle growth.
"Research suggests that exercise boosts levels of IGF-1 as well as other proteins that may be beneficial," Kaspar said. "Combining the two had a profound effect on survival and function, suggesting that the treatments together may make a significant difference in ALS progression."
But while this small study in mice shows promise, researchers still have a ways to go before human trials can begin. Nor can they say what kind of exercise may be best for someone with ALS.
Kaspar and his colleagues have already started the next phase of the mouse study, however - they are training mice to run on a treadmill. Training the animals will let the researchers control how long a mouse can exercise. They hope to be able to measure the effects of different durations of exercise on the disease.
"Understanding how exercise affects gene expression may help us find new therapies that slow down the progression of ALS," Kaspar said. The disease affects about 30,000 people in the United States, with roughly 5,000 new cases reported each year. Average life expectancy is five years from the onset of the disease.
The cause of ALS is unknown in all but 2 percent of cases, where the disease is caused by a known genetic mutation.
"The ultimate challenge is to figure out what triggers motor neuron death in the other 98 percent of people with the disease," Kaspar said.
Kaspar conducted the study with Soo Kim, a pre-doctoral fellow in biochemistry at Ohio State; with Liza Grissett and Priya Umapathi, both with Columbus Children's Research Institute; and with Lindsay Frost, Lindsey Christian and Fred Gage, all with the Salk Institute in La Jolla, Calif.
This work was supported by a grant from Project A.L.S the National Institutes of Health's National Institute of Neurological Disorders and Stroke.
Contact: Brian Kaspar, (614) 722-5085; Kasparb@ccri.net
Written by Holly Wagner, (614) 292-8310; Wagner.firstname.lastname@example.org